An intensive effort was directed at studying epidemiologic, virologic, immunologic and clinical aspects of the acquired immunodeficiency syndrome (AIDS). An ongoing study of 500 hospital employees has demonstrated the low risk of infection with the AIDS virus among hospital personnel. ELISA techniques have been developed for measuring isotype specific responses to proteins of the AIDS virus and these studies have demonstrated a better prognosis for those infected individuals who mount strong antibody responses to gag proteins. A cell line constitutively producing non-infectious AIDS virus was characterized and found to lack two of the polymerase proteins. A variety of non-lymphoid cell lines were found capable of supporting replication of the AIDS virus including colon cells. Virus was detected in multinucleated giant cells of the brains of patients with AIDS encephalopathy constituting the first demonstration of the precise cell type in the brain infected with the AIDS virus. Monoclonal antibodies directed against the AIDS virus were generated. The nature of the loss of antigen specific reactivity of the immune systems of patients with AIDS was further characterized by demonstrating a normal family of T cell receptor gene phenotypes and the presence of intact T cell receptor proteins on the surface of T cells obtained from patients with AIDS. The AIDS virus was found to be a potent polyclonal B cell activator. The nature of the immune response to the AIDS virus was examined utilizing systems for measuring antibody dependent cytotoxicity and cytotoxic T cells. A series of clinical trials were conducted in an attempt to improve the clinical status of patients with AIDS. The drug DHPG was studied in cytomegalovirus disease and trimetrexate studied in patients with pneumocystosis or toxoplasmosis. Among the anti-retroviral agents tested were suramin, HPA-23, foscarnet, and alpha interferon. Among the immunomodulatory approaches taken were interleukin-2 therapy and identical twin bone marrow transplantation coupled with peripheral lymphocyte transfers.